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Cells May 2022Hyperosmolality can occur during industrial fed-batch cultivation processes of Chinese hamster ovary (CHO) cells as highly concentrated feed and base solutions are added...
Hyperosmolality can occur during industrial fed-batch cultivation processes of Chinese hamster ovary (CHO) cells as highly concentrated feed and base solutions are added to replenish nutrients and regulate pH values. Some effects of hyperosmolality, such as increased cell size and growth inhibition, have been elucidated by previous research, but the impact of hyperosmolality and the specific effects of the added osmotic-active reagents have rarely been disentangled. In this study, CHO cells were exposed to four osmotic conditions between 300 mOsm/kg (physiologic condition) and 530 mOsm/kg (extreme hyperosmolality) caused by the addition of either high-glucose-supplemented industrial feed or mannitol as an osmotic control. We present novel single-cell cultivation data revealing heterogeneity in mass gain and cell division in response to these treatments. Exposure to extreme mannitol-induced hyperosmolality and to high-glucose-oversupplemented feed causes cell cycle termination, mtDNA damage, and mitochondrial membrane depolarization, which hints at the onset of premature stress-induced senescence. Thus, this study shows that both mannitol-induced hyperosmolality (530 mOsm/kg) and glucose overfeeding induce severe negative effects on cell growth and mitochondrial activity; therefore, they need to be considered during process development for commercial production.
Topics: Animals; CHO Cells; Cricetinae; Cricetulus; Glucose; Mannitol; Single-Cell Analysis
PubMed: 35681457
DOI: 10.3390/cells11111763 -
Gene Nov 2022Sorafenib is an FDA approved chemotherapeutic against hepatocellular carcinoma (HCC) yet associated with various resistance mechanisms. The role of high glucose status...
Sorafenib is an FDA approved chemotherapeutic against hepatocellular carcinoma (HCC) yet associated with various resistance mechanisms. The role of high glucose status on sorafenib action is still to be elucidated. This study clarifies such interaction, taking HepG2 cell lines as HCC models, MALAT1 and H19 as molecular players. HepG2 cell lines were purchased and classified into 8 groups. High glucose status was set by using d-glucose (33 mM) with insulin (1 µM). Mannitol (27.5 mM) was used as a negative osmotic control. Sorafenib was prepared at 15 µM and 20 µM. Cellular viability was assessed with MTT viability assay. Then, with trypan blue viability assay, the results were double checked and HepG2 morphology was examined by optical microscopy. MALAT1 and H19 RQs were assessed by real time PCR (RT-PCR). Results show that in comparison with sorafenib impact on HepG2, high glucose status drops cellular viability to 83.13 % (p < 0.01). With hyperosmolar mannitol, it decreases cellular viability to 72.89 % (p < 0.001). Regarding the molecular impact, hyperosmolar mannitol with sorafenib elevates both MALAT1 and H19 RQs. Yet, high glucose status elevates MALAT1and declines H19 (p < 0.05 and p < 0.001 for MALAT1 and H19 comparisons respectively). Therefore, the impact of high glucose status could be, in part, attributed to the hyperosmolar stress it induces on HepG2. Also, hyperosmolar mannitol, owing to its cytotoxic impact, is recommended for further confirmatory studies either as a separate therapeutic or as an adjuvant to sorafenib.
Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Line; Cell Line, Tumor; Cell Proliferation; Glucose; Hep G2 Cells; Humans; Liver Neoplasms; Mannitol; RNA, Long Noncoding; Sorafenib
PubMed: 35998844
DOI: 10.1016/j.gene.2022.146828 -
The Journal of Asthma : Official... Jul 2021Bronchial hyperresponsiveness (BHR) is a representative feature of asthma. Although methacholine and mannitol are commonly used for bronchial challenge tests, the... (Meta-Analysis)
Meta-Analysis
Diagnostic comparison of methacholine and mannitol bronchial challenge tests for identifying bronchial hyperresponsiveness in asthma: a systematic review and meta-analysis.
OBJECTIVE
Bronchial hyperresponsiveness (BHR) is a representative feature of asthma. Although methacholine and mannitol are commonly used for bronchial challenge tests, the optimal roles of the two agents for assessing BHR remain unclear. We compared the diagnostic performance of methacholine and mannitol in bronchial challenge tests.
METHODS
A systematic literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register. The sensitivity, specificity, diagnostic odds ratio (DOR), and a hierarchical summary of the receiver-operating characteristic curve (HSROC) of the two agents for detecting BHR in asthma were pooled using meta-analysis. A meta-regression analysis was used to identify potential sources of heterogeneity within the selected studies.
RESULTS
We identified six studies comprising 565 patients. The pooled sensitivity, specificity, and DOR of methacholine were 0.61 (95%CI, 0.44-0.76), 0.93 (95%CI, 0.70-0.99), and 23.47 (95% CI, 2.51-219.89), respectively. The pooled sensitivity, specificity, and diagnostic odds ratio of mannitol were 0.50 (95%CI, 0.28-0.73), 0.97 (95% CI, 0.94-0.99), and 35.22 (95% CI, 8.82-140.62), respectively. The area under the HSROC for mannitol was higher than that for methacholine (0.97 vs. 0.81, < 0.01). Considerable between-study heterogeneity was present for sensitivity and specificity in studies of both index tests. Univariate meta-regression analysis revealed that age and sex of the study participants were probable sources of heterogeneity for specificity in studies of methacholine.
CONCLUSION
Although mannitol showed better diagnostic performance than methacholine for identifying BHR in asthma, substantial between-study heterogeneity necessitates caution when interpreting the data.
Topics: Age Factors; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Humans; Mannitol; Methacholine Chloride; ROC Curve; Sensitivity and Specificity; Sex Factors
PubMed: 32138564
DOI: 10.1080/02770903.2020.1739704 -
Food Chemistry Oct 2022We present a qNMR method for the determination of low calories sweeteners (erythritol, mannitol, maltitol, sorbitol, isomalt and xylitol) in sugar-free foodstuff. The...
We present a qNMR method for the determination of low calories sweeteners (erythritol, mannitol, maltitol, sorbitol, isomalt and xylitol) in sugar-free foodstuff. The structural similarities of these compounds determine often a severe spectral overlap that hampers their quantification via conventional 1D and 2D NMR spectra. This problem is here overcome by exploiting the resolving capabilities of the CSSF-TOCSY experiment, allowing the quantification of all six polyols, with satisfactory results in terms of LoQ (2.8-7.4 mg/L for xylitol, mannitol, sorbitol, 15 mg/L for erythritol, 38 mg/L for maltitol and 91 mg/L for isomalt), precision (RSD% 0.40-4.03), trueness (bias% 0.15-4.81), and recovery (98-104%). Polyol's quantification in different sugar-free confectionary products was performed after a simple water extraction without any additional sample treatment. While these results demonstrate the robustness of the proposed method for polyols quantification in low calories foods, its applicability can be further extended to other food matrices or biofluids.
Topics: Carbohydrates; Erythritol; Mannitol; Polymers; Sorbitol; Sugar Alcohols; Xylitol
PubMed: 35569397
DOI: 10.1016/j.foodchem.2022.133125 -
American Journal of Kidney Diseases :... Oct 2019Intradialytic hypotension (IDH) is a common complication at the initiation of hemodialysis (HD) therapy, is associated with greater mortality, and may be related to... (Randomized Controlled Trial)
Randomized Controlled Trial
RATIONALE & OBJECTIVE
Intradialytic hypotension (IDH) is a common complication at the initiation of hemodialysis (HD) therapy, is associated with greater mortality, and may be related to relatively rapid shifts in plasma osmolality. This study sought to evaluate the effect of an intervention to minimize intradialytic changes in plasma osmolality on the occurrence of IDH.
STUDY DESIGN
Double-blind, single-center, randomized, controlled trial.
SETTING & PARTICIPANTS
Individuals requiring initiation of HD for acute or chronic kidney disease.
INTERVENTION
Mannitol, 0.25g/kg/h, versus a similar volume of 0.9% saline solution during the first 3 HD sessions.
OUTCOMES
The primary end point was average decline in systolic blood pressure (SBP). The secondary end point was the proportion of total sessions complicated by IDH (defined as a decrease ≥ 20mm Hg from the pre-HD SBP). Exploratory end points included biomarkers of cardiac and kidney injury.
RESULTS
52 patients were randomly assigned and contributed to 156 study visits. There were no significant differences in average SBP decline between the mannitol and placebo groups (15±11 vs 19±16mm Hg; P = 0.3). The proportion of total sessions complicated by IDH was lower in the mannitol group compared to placebo (25% vs 43%), with a nominally lower risk for developing an episode of IDH (OR, 0.38; 95% CI, 0.14-1.00), though this finding was of borderline statistical significance (P = 0.05). There were no consistent differences in cardiac and kidney injury biomarker levels between treatment groups.
LIMITATIONS
Modest sample size and number of events.
CONCLUSIONS
In this pilot randomized controlled trial studying patients requiring initiation of HD, we found no difference in absolute SBP decline between those who received mannitol and those who received saline solution. However, there were fewer overall IDH events and a nominally lower risk for dialysis sessions being complicated by IDH in the mannitol group. A larger multicenter randomized controlled trial is warranted.
FUNDING
Government funding to an author (Dr Mc Causland is supported by National Institute of Diabetes and Digestive and Kidney Diseases grant K23DK102511).
TRIAL REGISTRATION
Registered at ClinicalTrials.gov with study number NCT01520207.
Topics: Adult; Aged; Diuretics, Osmotic; Double-Blind Method; Female; Humans; Hypertonic Solutions; Hypotension; Kidney Failure, Chronic; Male; Mannitol; Middle Aged; Pilot Projects; Renal Dialysis
PubMed: 31040088
DOI: 10.1053/j.ajkd.2019.03.415 -
International Journal of Molecular... Sep 2022The present study induced prolonged hyperglycemia (a hallmark symptom of Type 2 diabetes [T2DM]) in (zebrafish) for eight or twelve weeks. The goal of this research was...
The present study induced prolonged hyperglycemia (a hallmark symptom of Type 2 diabetes [T2DM]) in (zebrafish) for eight or twelve weeks. The goal of this research was to study cognitive decline as well as vision loss in hyperglycemic zebrafish. Fish were submerged in glucose for eight or twelve weeks, after which they were assessed with both a cognitive assay (three-chamber choice) and a visual assay (optomotor response (OMR)). Zebrafish were also studied during recovery from hyperglycemia. Here, fish were removed from the hyperglycemic environment for 4 weeks after either 4 or 8 weeks in glucose, and cognition and vision was again assessed. The 8- and 12-week cognitive results revealed that water-treated fish showed evidence of learning while glucose- and mannitol-treated fish did not within the three-day testing period. OMR results identified an osmotic effect with glucose-treated fish having significantly fewer positive rotations than water-treated fish but comparable rotations to mannitol-treated fish. The 8- and 12-week recovery results showed that 4 weeks was not enough time to fully recovery from the hyperglycemic insult sustained.
Topics: Animals; Cognition; Cognitive Dysfunction; Diabetes Mellitus, Type 2; Glucose; Hyperglycemia; Mannitol; Water; Zebrafish
PubMed: 36077569
DOI: 10.3390/ijms231710167 -
The Annals of Thoracic Surgery Feb 2021
Topics: Glucose; Heart Transplantation; Humans; Mannitol; Potassium Chloride; Procaine; Tissue Donors
PubMed: 32593554
DOI: 10.1016/j.athoracsur.2020.05.034 -
ESC Heart Failure Apr 2023We analysed intestinal permeability in patients with chronic Chagas cardiomyopathy (CCC) and evaluated its association with clinical manifestations, haemodynamic...
AIMS
We analysed intestinal permeability in patients with chronic Chagas cardiomyopathy (CCC) and evaluated its association with clinical manifestations, haemodynamic parameters measured by echocardiogram, and disease outcome. Intestinal permeability was compared between CCC patients and a group of healthy controls.
BACKGROUND
Intestinal dysfunction may contribute to a more severe disease presentation with worse outcome in patients with CCC and heart failure.
METHODS
Fifty patients with CCC and left ventricular ejection fraction (LVEF) of less than 55% were prospectively selected and followed for a mean period of 18 ± 8 months. A group of 27 healthy volunteers were also investigated. One patient was excluded from the analysis since he died before completing the intestinal permeability test. Intestinal permeability was evaluated with the sugar probe drink test. It consists in the urinary recovery of previously ingested sugar probes: mannitol, a monosaccharide, and lactulose, a disaccharide.
RESULTS
Patient's mean age was 53.4 ± 10.4 years, and 31(63%) were male. Differential urinary excretion of lactulose/mannitol ratio did not differ significantly between healthy controls and CCC patients, regardless of clinical signs of venous congestion, haemodynamic parameters, and severity of presentation and outcome.
CONCLUSIONS
The present study could not show a disturbance of the intestinal barrier in CCC patients with LVEF <55%, measured by lactulose/mannitol urinary excretion ratio. Further investigations are needed to verify if in patients with LVEF <40% intestinal permeability is increased.
Topics: Humans; Male; Adult; Middle Aged; Female; Lactulose; Stroke Volume; Ventricular Function, Left; Mannitol; Permeability; Heart Failure; Chronic Disease
PubMed: 36708272
DOI: 10.1002/ehf2.14156 -
Transplantation Proceedings Sep 2021The effect of mannitol usage during kidney donation and kidney transplantation is still unclear. Therefore, we performed a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effect of mannitol usage during kidney donation and kidney transplantation is still unclear. Therefore, we performed a systematic review and meta-analysis to research the difference in graft function between kidney grafts treated with and without mannitol.
METHODS
A literature search was performed in 5 databases and included 8 eligible studies out of 3570 references, which were included up to July 12, 2021. Relevant outcomes for analysis were graft survival, rejection, acute renal failure, delayed graft function, renal failure, creatinine clearance, diuresis, and serum creatinine.
RESULTS
Eight studies were identified, 1 study examining the effect of mannitol during kidney donation and 7 studies during kidney transplantation, of which 6 eligible for meta-analysis. A total of 1143 patients were included in these studies. The following outcome measures demonstrated significant differences in favor of mannitol usage compared with a control group: acute renal failure (risk ratio [RR], 0.45; 95% confidence interval [CI], 0.26-0.79; P < .01]) and delayed graft function (RR, 0.25; 95% CI, 0.08-0.77; P = 0.02 and RR, 0.69; 95% CI, 0.51-0.94; P = 0.94). Differences in other outcome parameters were not significant.
CONCLUSIONS
This systematic review and meta-analysis suggested that the use of mannitol during kidney transplantation leads to lower incidence of acute renal failure and delayed graft function. For all other outcomes, no significant difference was found. Further research should be conducted on the use of mannitol during donor nephrectomy because of the limited availability of studies. Finally, for interpretation of the outcomes, the quality of the evidence should be taken into consideration and we emphasize the need for more up-to-date research.
Topics: Graft Rejection; Graft Survival; Humans; Kidney; Kidney Transplantation; Mannitol
PubMed: 34412911
DOI: 10.1016/j.transproceed.2021.07.001 -
Drug Delivery and Translational Research Feb 2024Pulmonary delivery of mRNA via inhalation is a very attractive approach for RNA-based therapy for treatment of lung diseases. In this work, we have demonstrated...
Pulmonary delivery of mRNA via inhalation is a very attractive approach for RNA-based therapy for treatment of lung diseases. In this work, we have demonstrated successful development of an mRNA-lipid nanoparticle (LNP) dry powder product (DPP), wherein the LNPs were spray dried using hydroalcoholic solvent along with mannitol and leucine as excipients. The desired critical attributes for the DPP were accomplished by varying the excipients, lipid composition, concentration of LNPs, and weight percentage of mRNA. Leucine alone or in combination with mannitol improved the formulation by increasing the mRNA yield as well as decreasing the particle size. Intratracheal administration of the DPP in mice resulted in luciferase expression in the trachea and lungs indicating successful delivery of functional mRNA. Our results show formulation optimization of mRNA LNPs administered in the form of DPP results in an efficacious functional delivery with great promise for future development of mRNA therapeutics for lung diseases.
Topics: Mice; Animals; Powders; RNA, Messenger; Excipients; Leucine; Lung; Nanoparticles; Mannitol; Lung Diseases; Particle Size
PubMed: 37526881
DOI: 10.1007/s13346-023-01402-y